In the ongoing fight against disease, new and improved methods for stimulating the immune system are continually being sought. Augmentation of the immune system is required, as it is not always possible to have an immunity before contracting a disease, and it may be too late to react successfully against the disease once the symptoms have manifested.
Accordingly, significant amounts of research have been dedicated to establishing and finding substances which will give an advantage against an infection. Prime amongst these is the use of vaccines but, unfortunately, the substances against which it is desired to generate an immunity do not always prove immunogenic, or are only weakly immunogenic and cannot be used to generate an adequate immune response.
Accordingly, attention has focused on synthetic substances to promote a response against disease, and various classes of substance have been found. Amongst these classes are the adjuvants, the immune stimulants and the carriers.
Adjuvants are used to boost an immune response against a vaccine, and may even be used to stimulate an immune response against an otherwise non-immunogenic antigen. A typical example of an adjuvant is Freund's Complete Adjuvant (FCA). This adjuvant works very well in animals, but leads to significant swelling and pain in humans, and cannot be used. There exist adjuvants which can be used in human medicine, such as aluminium salts, but the choice is somewhat restricted, and the available adjuvants tend not to be particularly effective.
Immune stimulators are those compounds which stimulate the immune system, even in the absence of suitable antigenic material. Many such substances have been identified, but such compounds tend to be toxic, and cannot easily be catabolized. An example of such a substance is polyvinylpyrrolidone.
Carrier substances are generally proteins which are complexed or conjugated with an antigen or hapten and, by virtue of the association with the antigen or hapten, can cause an immune response to be generated where otherwise there would be none. The problem with this system is that the carrier protein must be so selected as not to be antigenic itself.
It will be appreciated, therefore, that there is considerable demand for new substances which can successfully be used in any of the above categories. We have now discovered that a series of quaternary salts of polyheterocyclic compounds is useful in all of the above categories.